Journal of Alzheimer's Disease - Volume 100, issue 1

Authors: Al-Hammadi, Mustafa | Fleyeh, Hasan | Åberg, Anna Cristina | Halvorsen, Kjartan | Thomas, Ilias

Article Type: Systematic Review

Abstract: Background: Dementia is a general term for several progressive neurodegenerative disorders including Alzheimer’s disease. Timely and accurate detection is crucial for early intervention. Advancements in artificial intelligence present significant potential for using machine learning to aid in early detection. Objective: Summarize the state-of-the-art machine learning-based approaches for dementia prediction, focusing on non-invasive methods, as the burden on the patients is lower. Specifically, the analysis of gait and speech performance can offer insights into cognitive health through clinically cost-effective screening methods. Methods: A systematic literature review was conducted following the PRISMA protocol (Preferred Reporting Items for Systematic …Reviews and Meta-Analyses). The search was performed on three electronic databases (Scopus, Web of Science, and PubMed) to identify the relevant studies published between 2017 to 2022. A total of 40 papers were selected for review. Results: The most common machine learning methods employed were support vector machine followed by deep learning. Studies suggested the use of multimodal approaches as they can provide comprehensive and better prediction performance. Deep learning application in gait studies is still in the early stages as few studies have applied it. Moreover, including features of whole body movement contribute to better classification accuracy. Regarding speech studies, the combination of different parameters (acoustic, linguistic, cognitive testing) produced better results. Conclusions: The review highlights the potential of machine learning, particularly non-invasive approaches, in the early prediction of dementia. The comparable prediction accuracies of manual and automatic speech analysis indicate an imminent fully automated approach for dementia detection. Show more

Keywords: Alzheimer’s disease, cognitive impairment, deep learning, dementia disorders, gait analysis, machine learning, non-invasive, speech analysis

DOI: 10.3233/JAD-231459

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 1-27, 2024

Authors: Meng, Hongyan | Lv, Xiangru | Zhang, Rong | Feng, Yuping | Wang, Jing | Liu, Jiarui | Zhang, Juxia

Article Type: Systematic Review

Abstract: Background: To date, the magnitude of association and the quality of evidence for cognitive decline (mild cognitive impairment, Alzheimer’s disease, and dementia) in couples and risk factors for outcomes have not been reviewed and analyzed systematically. Objective: The aim of this study was to investigate the concordance of cognitive impairment in unrelated spouses and to qualitatively describe potential risk factors. Methods: Eight databases were searched from inception to October 20, 2023. Eligible studies were independently screened and assessed for quality. Statistical analysis was conducted using Stata 15.1 software. The study was preregistered with PROSPERO (CRD42023488024). …Results: Eleven studies involving couples were included, with moderate to high evidence quality. Compared to controls, spouses of individuals with cognitive impairment had lower cognitive scores (Cohen’s d : 0.18-0.62) and higher risk of cognitive decline (OR  = 1.42, 95% CI : 1.15–1.76). The consistency of cognitive impairment between spouses was attributed to three theories: 1) the impact of caregiving stress experienced by the spouse; 2) assortative mating, which suggests that individuals select partners with similar characteristics; and 3) the influence of shared living environments and lifestyles. Conclusions: The cognitive status of one spouse can affect the cognitive function of the other spouse. It is important to consider shared lifestyle, environmental, and psychobehavioral factors, as they may contribute to the risk of cognitive decline by couples. Identifying these factors can inform the development of targeted recommendations for interventions and preventive measures. Show more

Keywords: Alzheimer’s disease, cognitive decline, dementia, meta-analysis, risk factor, spouses concordance, systematic review

DOI: 10.3233/JAD-240325

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 29-40, 2024

Authors: Cantero-Fortiz, Yahveth | Cano, Amanda | Boada, Mercè

Article Type: Article Commentary

Abstract: This commentary provides an in-depth analysis of a recently published systematic review on ‘Biomarkers of Tau Pathology in Alzheimer’s Disease’, elucidating insights into its implications for the field. This meta-analysis highlights the potential of plasma and CSF p-tau 181/231 as promising, non-invasive, and cost-effective diagnostic tools for patients suffering from AD continuum. The study comprehensively reviews the diagnostic potential of these p-tau isoforms, shedding light on their role in the precision diagnosis of Alzheimer’s disease. Here we discuss the significance of these findings and the methodological nuances, emphasizing broader implications for advancing personalized medicine in neurodegenerative disorders.

Keywords: Alzheimer’s disease, biomarkers, precision medicine, tau pathology

DOI: 10.3233/JAD-240055

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 41-43, 2024

Authors: Getasew Hiruy, Endalk | Woldegiorgis Abate, Teshager | Animaw Temesgen, Worku | Bantie, Berihun | Kassaw Yirga, Gebrie | Nuru Muhamed, Ahmed | Mitiku Shiferaw, Sahilu | Misganaw Kebede, Worku | Minwuyelet Yitayew, Fentahun | Walelgn Dessalegn, Nigusie

Article Type: Research Article

Abstract: Background: Neurocognitive impairment, characterized by reduced performance in various cognitive domains, has been significantly linked with glycemic control in type 2 diabetes mellitus (T2DM) patients. Poorly controlled diabetes often results in decreased cognitive abilities, and a longer duration of the disease is associated with lower cognitive levels. Objective: This study aimed to evaluate the prevalence of cognitive impairment in adults with T2DM and identify related factors. Methods: An institution-based cross-sectional study was conducted among 421 adults with T2DM. A systematic random sampling was used to select study participants in two referral hospitals in Bahir Dar, Ethiopia. …Standardized Mini-Mental State Examination tool was used. Binary logistic regression was used. Significance was declared at p value≤0.05 with 95% confidence interval. Results: Over a quarter (27.6%) of participants were identified as cognitively impaired. Factors associated with lower cognitive status included older age, being single, lower education level, farming occupation, presence of comorbidity, and engagement in moderate physical activity. Conclusions: In conclusion, the prevalence of cognitive impairment among T2DM patients is a growing concern. Several risk factors have been identified like age group, marital status, education level, occupation, presence of comorbidity, and moderate physical activities. The impact of cognitive impairment on the quality of life and functional abilities of T2DM patients should not be underestimated. Show more

Keywords: Alzheimer’s disease, associated factors, cognitive impairment, Ethiopia, type 2 diabetes mellitus

DOI: 10.3233/JAD-230245

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 45-52, 2024

Authors: Zukowski, Lisa A. | Brinkerhoff, Sarah A. | Levin, Ilana | Herter, Troy M. | Hetrick, Lena | Lockhart, Samuel N. | Miller, Michael E. | Laurienti, Paul J. | Kritchevsky, Stephen B. | Hugenschmidt, Christina E.

Article Type: Research Article

Abstract: Background: A screening tool sensitive to Alzheimer’s disease (AD) risk factors, such as amyloid-β (Aβ) deposition, and subtle cognitive changes, best elicited by complex everyday tasks, is needed. Objective: To determine if grocery shopping performance could differentiate older adults at elevated risk of developing AD (OAer), older adults at low risk of developing AD (OAlr), and young adults (YA), and if amount of Aβ deposition could predict grocery shopping performance in older adults (OA). Methods: Twenty-one OAer (78±5 years), 33 OAlr (78±5 years), and 28 YA (31±3 years) performed four grocery shopping trials, with the best …and worst performances analyzed. Measures included trial time, number of correct items, number of grocery note fixations, and number of fixations and percentage of time fixating on the correct shelving unit, correct brand, and correct shelf. Linear mixed effects models compared measures by performance rank (best, worst) and group (OAer, OAlr, YA), and estimated the effect of Aβ deposition on measures in OA. Results: Relative to their best performance, OAer and OAlr exhibited more correct shelving unit fixations and correct brand fixations during their worst performance, while YA did not. Within OA’s worst performance, greater Aβ deposition was associated with a smaller percentage of time fixating on the correct shelving unit, correct shelf, and correct brand. Within OA, greater Aβ deposition was associated with more grocery note fixations. Conclusions: OA with elevated Aβ deposition may exhibit subtle working memory impairments and less efficient visual search strategies while performing a cognitively demanding everyday task. Show more

Keywords: Alzheimer’s disease, cognition, eye-tracking, visual processing

DOI: 10.3233/JAD-231108

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 53-75, 2024

Authors: Shi, Qin | Liu, Wei-Shi | Liu, Fang | Zeng, Yi-Xuan | Chen, Shu-Fen | Chen, Ke-Liang | Yu, Jin-Tai | Huang, Yu-Yuan

Article Type: Research Article

Abstract: Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within …6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer’s disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer’s disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation. Show more

Keywords: Alzheimer’s disease, cognitive impairment, neurodegenerative causes, non-neurodegenerative causes, rapidly progressive dementia, spectrum

DOI: 10.3233/JAD-240079

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 77-85, 2024

Authors: Dombrowski, Wen | Mims, Adrienne | Kremer, Ian | Cano Desandes, Pedro | Rodrigo-Herrero, Silvia | Epps, Fayron | Snow, Teepa | Gutierrez, Myrna | Nasta, Anil | Epperly, Mikele Bunce | Manaloto, Katrina | Hansen, Jennie Chin

Article Type: Research Article

Abstract: Background: Globally, much work has been done by nonprofit, private, and academic groups to develop best practices for the care of people living with dementia (PLWD), including Alzheimer’s disease. However, these best practices reside in disparate repositories and tend to focus on one phase of the patient journey or one relevant group. Objective: To fill this gap, we developed a Dementia Ideal Care Map that everyone in the dementia ecosystem can use as an actionable tool for awareness, policy development, funding, research, training, service delivery, and technology design. The intended audience includes (and not limited to) policymakers, academia, …industry, technology developers, health system leaders, clinicians, social service providers, patient advocates, PLWD, their families, and communities at large. Methods: A search was conducted for published dementia care best practices and quality measures, which were then summarized in a visual diagram. The draft diagram was analyzed to identify barriers to ideal care. Then, additional processes, services, technologies, and quality measures to overcome those challenges were brainstormed. Feedback was then obtained from experts. Results: The Dementia Ideal Care Map summarizes the ecosystem of over 200 best practices, nearly 100 technology enablers, other infrastructure, and enhanced care pathways in one comprehensive diagram. It includes psychosocial interventions, care partner support, community-based organizations; awareness, risk reduction; initial detection, diagnosis, ongoing medical care; governments, payers, health systems, businesses, data, research, and training. Conclusions: Dementia Ideal Care Map is a practical tool for planning and coordinating dementia care. This visualized ecosystem approach can be applied to other conditions. Show more

Keywords: Alzheimer’s disease, caregivers, critical pathways, digital health, health policy, health promotion, practice guidelines as topic, quality of health care, social support, stakeholder participation

DOI: 10.3233/JAD-231491

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 87-117, 2024

Authors: Li, Jian-Guo | Mutreja, Yamini | Servili, Maurizio | Leone, Alessandro | Praticò, Domenico

Article Type: Research Article

Abstract: Background: Chronic intake of extra virgin olive oil is beneficial for brain health and protects from age-related cognitive decline and dementia, whose most common clinical manifestation is Alzheimer’s disease. Besides the classical pathologic deposits of amyloid beta peptides and phosphorylated tau proteins, another frequent feature of the Alzheimer’s brain is neuroinflammation. Objective: In the current study, we assessed the effect that extra virgin olive oil has on neuroinflammation when administered to a mouse model of the disease. Methods: Triple transgenic mice were randomized to receive a diet enriched with extra virgin olive oil or regular diet …for 8 weeks. At the end of this treatment period the expression level of several inflammatory biomarkers was assessed in the central nervous system. Results: Among the 79 biomarkers measured, compared with the control group, mice receiving the extra virgin olive oil had a significant reduction in MIP-2, IL-17E, IL-23, and IL-12p70, but an increase in IL-5. To validate these results, specific ELISA kits were used for each of them. Confirmatory results were obtained for MIP-2, IL-17E, IL-23, and IL-12-p70. No significant differences between the two groups were observed for IL-5. Conclusions: Our results demonstrate that chronic administration of extra virgin olive oil has a potent anti-neuroinflammatory action in a model of Alzheimer’s disease. They provide additional pre-clinical support and novel mechanistic insights for the beneficial effect that this dietary intervention has on brain health and dementia. Show more

Keywords: Alzheimer’s disease, cytokines, extra-virgin olive oil, Mediterranean diet, neuroinflammation, transgenic mice

DOI: 10.3233/JAD-240374

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 119-126, 2024

Authors: Tang, Zhihui | Hirano, Shigeki | Koizumi, Yume | Izumi, Michiko | Kitayama, Yoshihisa | Yamagishi, Kosuke | Tamura, Mitsuyoshi | Ishikawa, Ai | Kashiwado, Kouichi | Iimori, Takashi | Mukai, Hiroki | Yokota, Hajime | Horikoshi, Takuro | Uno, Takashi | Kuwabara, Satoshi

Article Type: Research Article

Abstract: Background: Dementia with Lewy bodies (DLB) presents with various symptoms, posing challenges for early diagnosis challenging. Dopamine transporter (123 I-FP-CIT) single-photon emission tomography (SPECT) and 123 I-meta-iodobenzylguanidine (123 I-MIBG) imaging are crucial diagnostic biomarkers. Hypothesis about body- and brain-first subtypes of DLB indicate that some DLB may show normal 123 I-FP-CIT or 123 I-MIBG results; but the characteristic expression of these two subtypes remains unclear. Objective: This study aimed to evaluate the diagnostic sensitivity of 123 I-FP-CIT and 123 I-MIBG imaging alone, combined in patients with DLB and explore symptoms associated with the abnormal imaging results. …Methods: Demographic data, clinical status, and imaging results were retrospectively collected from patients diagnosed with possible DLB. Both images were quantified using semi-automated software, and the sensitivity of each imaging modality and their combination was calculated. Demographic data, cognition, and motor and non-motor symptoms were compared among the subgroups based on the imaging results. Symptoms related to each imaging abnormality were examined using binomial logistic regression analyses. Results: Among 114 patients with DLB, 80 underwent 123 I-FP-CIT SPECT (sensitivity: 80.3%), 83 underwent 123 I-MIBG imaging (68.2%), and 66 both (sensitivity of either abnormal result: 93.9%). Visual hallucinations differed among the four subgroups based on imaging results. Additionally, nocturia and orthostatic hypotension differed between abnormal and normal 123 I-MIBG images. Conclusions: Overall, 123 I-FP-CIT SPECT was slightly higher sensitivity than 123 I-MIBG imaging, with combined imaging increasing diagnostic sensitivity. Normal results of a single imaging test may not refute DLB. Autonomic symptoms may lead to abnormal 123 I-MIBG scintigraphy findings indicating body-first subtype of patients with DLB. Show more

Keywords: Alzheimer’s disease, dementia with Lewy bodies, dopamine transporter imaging, 123I-meta-iodobenzylguanidine myocardial scintigraphy, sensitivity, SPECT

DOI: 10.3233/JAD-231395

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 127-137, 2024

Authors: Taylor, Jack | Jaros, Mark | Chen, Christopher | Harrison, John | Hilt, Dana

Article Type: Research Article

Abstract: Background: Blood biomarkers are proposed as a diagnostic alternative to amyloid PET or cerebrospinal fluid (CSF) analyses for the diagnosis of Alzheimer’s disease (AD). Relatively little is known of the natural history of patients identified by different blood biomarkers. Objective: To identify patients with elevated plasma phosphorylated tau (pTau)181 from a prior Phase 2a trial, and explore the natural histories of their clinical progression, and potential efficacy of Xanamem, a selective inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these patients. Methods: A prespecified, double-blind analysis was conducted in 72 participants with clinically diagnosed AD and …available plasma samples from baseline and Week 12 of the “XanADu” Phase 2a trial of Xanamem versus placebo. The analysis prespecified plasma pTau181 > median to identify patients more likely to have AD (“H”, > 6.74 pg/mL, n  = 34). Cohen’s d (d ) of≥0.2 defined potential clinical significance. Results: In the placebo group, H patients showed greater clinical progression compared to L patients (pTau181≤median) on ADCOMS (d  = 0.55, p  < 0.001), CDR-SB (d  = 0.63, p  < 0.001), MMSE (d  = 0.52, p  = 0.12), and ADAS-Cog14 (d  = 0.53, p  = 0.19). In H patients, a potentially clinically meaningful Xanamem treatment effect compared to placebo was seen in the CDR-SB (LS mean difference 0.6 units, d  = 0.41, p  = 0.09) and Neuropsychological Test Battery (NTB; LS mean difference 1.8 units, d  = 0.26, p  = 0.48) but not ADCOMS or ADAS-Cog14. Conclusions: This trial demonstrates that elevated plasma pTau181 identifies participants more likely to have progressive AD and is a suitable method for enrichment in AD clinical trials. Xanamem treatment showed evidence of potential clinically meaningful benefits. Show more

Keywords: Alzheimer’s disease, 11-beta-Hydroxysteroid Dehydrogenase Type 1, blood biomarker, cortisol, drug development, pTau181

DOI: 10.3233/JAD-231456

Citation: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 139-150, 2024